DESCRIPTION (Investigator's Abstract): Cryptococcus neoformans is the etiologic agent of cryptococcosis, one of the most serious global fungal disease and one of the most common pathogens isolated from the central nervous system in the world today. It is clear that over the last two decades as immunocompromised populations rise, the explosion of cases of cryptococcosis in all areas of the wold have been impressive. The ecnonomic impact of C. neoformans on health care systems is overhwelming, since there is presently no cure for AIDS and costly life-long anti-fungal prophylaxis or maintenance therapy (once infected) is required for these patients. Because of prolonged maintenance therapies with anti-fungal drugs, isolations of drug-resistant strains have been increasing. In this application we propose to build upon ongoing efforts of Drs. Ron Davis and Richard Hyman at Stanford University to provide 4-5X sequence coverage of the C. neoformans genome to generate an additional 4X sequence coverage, assemble all of the C. neoformans sequence data generated at Stanford and TIGR and complete gap closure on all or most of the C. neoformans genome. We will then use a variety of computer methods to identify all open reading frames (ORFs) in the C. neoformans genome sequence and identify as many as ORFs as possible to proteins of known function. Once sequenced, the C. neoformans genome will be the firsts publicly available for a Basidiomycetes. Since C. neoformans is phylogenetically at the junction between some of the most destructive plant pathogens (such as smuts or rusts) and economically important food sources (mushrooms) within the Basidiomycota, interest in the sequence data will extend from the medical community to the agricultural industry. Because C. neoformans will be the model organism for all other basidiomycetes, it is crucial that a relatively complete genome sequence be publically available for other areas to build their sequencing efforts upon.